PFAS Exposure and Male Reproductive Health: Implications for Sperm Epigenetics.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants found in human tissues and persist in the environment, posing significant risks to reproductive health. This review examines the impact of PFAS exposure on male reproductive health, with a focus on sperm epigenetics. PFASs disrupt endocrine function by altering key reproductive hormones and impairing sperm motility, quality, and viability.

Development of a framework to structure decision-making in environmental and occupational health: A systematic review and Delphi study.

Background: Environmental and occupational health (EOH) assessments increasingly utilize systematic review methods and structured frameworks for evaluating evidence about the human health effects of exposures. However, there is no prevailing approach for how to integrate this evidence into decisions or recommendations. Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision (EtD) frameworks provide a structure to support standardized and transparent consideration of relevant criteria to inform health decisions.

Bayesian Gene Set Benchmark Dose Estimation for "omic" responses.

Motivation: Estimating a toxic reference point using tools like the benchmark dose (BMD) is a critical step in setting policy to regulate pollution and ensure safe environments. Toxicity can be measured for different endpoints, including changes in gene expression and histopathology for various tissues, and is typically explored one gene or tissue at a time in a univariate setting that ignores correlation. In this work, we develop a multivariate estimation procedure to estimate the BMD for specified gene sets.

Public Health.

Background: Pesticide exposure may contribute to cognitive decline, but empirical evidence is limited. We examined high pesticide exposure events (HPEE) in relation to subjective cognitive decline among farmers in the Pesticide and Sense of Smell Study (PASS), a sub-cohort of the Agricultural Health Study (AHS).

Method: This analysis included 2365 predominantly white male farmers from Iowa and North Carolina (aged 70±10 years) who enrolled in AHS from 1993-1997 and participated in PASS in 2020-2021.

Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.

Prenatal Perfluoroalkyl Substance Exposure in Association with Global Histone Post-Translational Methylation in 2-Year-Old Children.

Perfluoroalkyl substances (PFASs) have elimination half-lives in years in humans and are persistent in the environment. PFASs can cross the placenta and impact fetal development. Exposure to PFASs may lead to adverse effects through epigenetic mechanisms.

A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma.

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype.

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.

Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response.

Fluoride Exposure and Children's IQ Scores: A Systematic Review and Meta-Analysis.

Importance: Previous meta-analyses suggest that fluoride exposure is adversely associated with children's IQ scores. An individual's total fluoride exposure comes primarily from fluoride in drinking water, food, and beverages.

Objective: To perform a systematic review and meta-analysis of epidemiological studies investigating children's IQ scores and prenatal or postnatal fluoride exposure.

Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.

Coronaviruses evade detection by the host immune system with the help of the endoribonuclease Nsp15, which regulates levels of viral double stranded RNA by cleaving 3' of uridine (U). While prior structural data shows that to cleave double stranded RNA, Nsp15's target U must be flipped out of the helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously flipped bases. We address this gap by designing fluorinated double stranded RNA substrates that allow us to directly relate a U's sequence context to both its tendency to spontaneously flip and its susceptibility to cleavage by Nsp15.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Proximity to petrochemical industry and risk of childhood asthma occurrence.

Adverse effects on the respiratory system were associated with intensive petroleum-related industrial activities. The study aimed to assess the impact of petrochemical exposure on childhood asthma using various surrogate indices. A singleton birth cohort from 2004 to 2017 was conducted, leveraging two linked nationwide databases in Taiwan.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3'UTR.

Estimated exposure to endotoxin and circulating immunological markers among male farmers in the Biomarkers of Exposure and Effect in Agriculture study.

Background: Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin.

Detection of Movement and Lead-Popping Artifacts in Polysomnography EEG Data.

Polysomnography (PSG) measures brain activity during sleep via electroencephalography (EEG) using six leads. Artifacts caused by movement or loose leads distort EEG measurements. We developed a method to automatically identify such artifacts in a PSG EEG trace.

Perineuronal nets on CA2 pyramidal cells and parvalbumin-expressing cells differentially regulate hippocampal dependent memory.

Perineuronal nets (PNNs) are a specialized extracellular matrix that surround certain populations of neurons, including (inhibitory) parvalbumin (PV) expressing-interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells.

Concentrations, composition profiles, and in vitro-in silico-based mixture risk assessment of bisphenol A and its analogs in plant-based foods.

The substitution of bisphenol A (BPA) with structurally similar analogs has raised concerns due to their comparable estrogenic activities. Considering the high consumption of plant-based foods, assessing the risks posed by bisphenols (BPs) in such dietary sources is essential. However, limited exposure and animal toxicological data on BP analogs hinder comprehensive risk assessments.

Identification of a Potent CDK8 Inhibitor Using Structure-Based Virtual Screening.

Pulmonary fibrosis is excessive scarring of the lung tissues. Transforming growth factor-beta (TGF-β) has been implicated in pulmonary fibrosis due to its ability to induce the epithelial-to-mesenchymal transition (EMT) and promote epithelial cell migration. Cyclin-dependent kinase 8 (CDK8) can mediate the TGF-β signaling pathways and could function as an alternative therapeutic target for treating pulmonary fibrosis.

Association of early-life trauma with gestational diabetes and hypertensive disorders of pregnancy.

Background: Early-life trauma (before age 18) is hypothesized to increase risk for adverse pregnancy outcomes through stress pathways, yet epidemiologic findings are mixed.

Methods: Sister Study participants (U.S.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Volatile hydrocarbon exposures and immune-related illnesses among Deepwater Horizon oil spill workers.

Background: Despite evidence from experimental studies linking some petroleum hydrocarbons to markers of immune suppression, limited epidemiologic research exists on this topic.

Objective: The aim of this cross-sectional study was to examine associations of oil spill related chemicals (benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H)) and total hydrocarbons (THC) with immune-related illnesses as indicators of potential immune suppression.

Methods: Subjects comprised 8601 Deepwater Horizon (DWH) oil spill clean-up and response workers who participated in a home visit (1-3 years after the DWH spill) in the Gulf Long-term Follow-up (GuLF) Study.